The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion
| Autor: | Rocha, Nuno, Payne, Felicity, Huang-Doran, Isabel, Sleigh, Alison, Fawcett, Katherine, Adams, Claire, Stears, Anna, Saudek, Vladimir, O'Rahilly, Stephen, Barroso, Inês, Semple, Robert K |
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| Přispěvatelé: | Sleigh, Alison [0000-0002-3859-8701], O'Rahilly, Stephen [0000-0003-2199-4449], Barroso, Inês [0000-0001-5800-4520], Semple, Robert K [0000-0001-6539-3069], Apollo - University of Cambridge Repository |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Lipodystrophy lcsh:Medicine Golgi Apparatus Haploinsufficiency Article Mice Young Adult 3T3-L1 Cells Journal Article Adipocytes Animals Humans lcsh:Science Metabolic Syndrome Adipogenesis ADP-Ribosylation Factors lcsh:R Cell Differentiation Middle Aged Protein Transport HEK293 Cells Gene Expression Regulation Gene Knockdown Techniques lcsh:Q Female Adiponectin Insulin Resistance |
| Zdroj: | Scientific Reports Rocha, N, Payne, F, Huang-Doran, I, Sleigh, A, Fawcett, K, Adams, C, Stears, A, Saudek, V, O'Rahilly, S, Barroso, I & Semple, R K 2017, ' The metabolic syndrome-associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion ', Scientific Reports, vol. 7, no. 1, pp. 17593 . https://doi.org/10.1038/s41598-017-17746-8 Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-17746-8 |
| Popis: | Common genetic variants at the ARL15 locus are associated with plasma adiponectin, insulin and HDL cholesterol concentrations, obesity, and coronary atherosclerosis. The ARL15 gene encodes a small GTP-binding protein whose function is currently unknown. In this study adipocyte-autonomous roles for ARL15 were investigated using conditional knockdown of Arl15 in murine 3T3-L1 (pre)adipocytes. Arl15 knockdown in differentiated adipocytes impaired adiponectin secretion but not adipsin secretion or insulin action, while in preadipocytes it impaired adipogenesis. In differentiated adipocytes GFP-tagged ARL15 localized predominantly to the Golgi with lower levels detected at the plasma membrane and intracellular vesicles, suggesting involvement in intracellular trafficking. Sequencing of ARL15 in 375 severely insulin resistant patients identified four rare heterozygous variants, including an early nonsense mutation in a proband with femorogluteal lipodystrophy and non classical congenital adrenal hyperplasia, and an essential splice site mutation in a proband with partial lipodystrophy and a history of childhood yolk sac tumour. No nonsense or essential splice site mutations were found in 2,479 controls, while five such variants were found in the ExAC database. These findings provide evidence that ARL15 plays a role in adipocyte differentiation and adiponectin secretion, and raise the possibility that human ARL15 haploinsufficiency predisposes to lipodystrophy. |
| Databáze: | OpenAIRE |
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